Resuscitation enhancements

ABSTRACT

A system including a sensor interface coupled to a processor. The sensor interface is configured to receive and process an analog electrocardiogram signal of a subject and provide a digitized electrocardiogram signal sampled over a first time period and a second time period that is subsequent to the first time period. The processor is configured to receive the digitized electrocardiogram signal, to analyze a frequency domain transform of the digitized electrocardiogram signal sampled over the first and second time periods and determine first and second metrics indicative of metabolic state of a myocardium of the subject during the first and second time periods, respectively, to compare the first and second metrics to determine whether the metabolic state of the myocardium of the subject is improving, and to indicate administration of an intervention to the subject in response to a determination that the metabolic state is not improving.

BACKGROUND OF INVENTION

1. Field of Invention

Aspects and embodiments of the present invention are directed to the useof spectral analysis of Ventricular Fibrillation (VF) waveforms to aidin the resuscitation of a subject experiencing cardiac arrest.

2. Background

Cardiac arrest is a major cause of death worldwide. Variousresuscitation efforts aim to maintain the body's circulatory andrespiratory systems during cardiac arrest in an attempt to save the lifeof the subject. Such resuscitation efforts may include CPR (i.e., chestcompressions with or without artificial respiration), defibrillation,drug therapy, open heart massage, or various combinations thereof. Formany forms of cardiac arrest, such as where the subject is sufferingfrom Ventricular Fibrillation (VF) or Ventricular Tachycardia (VT),defibrillation may be appropriate, especially if applied soon after theonset of VF or VT. However, because defibrillation can itself causemyocardial injury, it should generally be applied only when there is asufficient probability of success that it will be successful inrestoring a perfusing cardiac rhythm.

U.S. Pat. No. 5,957,856 (hereinafter the '856 patent), which isincorporated by reference in its entirety herein, discloses a system andmethod for predicting the success of a defibrillating shock based upon aspectral analysis of VF waveforms obtained from an electrocardiogram(ECG) of the subject. As described therein, various metrics, such as theaverage peak-to-trough amplitude (AM) of the VF waveform, the area ofthe amplitude spectrum (ASA or AMSA) of the VF waveform, the medianfrequency of the power spectrum of the VF waveform, or the area of thepower spectrum (PSA) of the VF waveform may be used to predict whendefibrillation is likely to be successful in restoring a perfusingcardiac rhythm, as well as when defibrillation is likely to not besuccessful.

SUMMARY

In accordance with one aspect of the present invention, a system isprovided that includes a sensor interface and a processor. The sensorinterface is configured to receive and process an analogelectrocardiogram signal of the subject and provide a digitizedelectrocardiogram signal sampled over a first time period and a secondtime period that is subsequent to the first time period. The processoris coupled to the sensor interface and is configured to receive thedigitized electrocardiogram signal, to analyze a frequency domaintransform of the digitized electrocardiogram signal sampled over thefirst time period and the second time period and determine first andsecond metrics indicative of metabolic state of a myocardium of thesubject during the first and second time periods, respectively, tocompare the first and second metrics to determine whether the metabolicstate of the myocardium of the subject is improving, and to indicateadministration of a thrombolytic agent to the subject in response to adetermination that the metabolic state of the myocardium of the subjectis not improving.

In accordance with another aspect of the present invention, a method isprovided. The method comprises receiving an electrocardiogram signal;analyzing a first frequency domain transform of the electrocardiogramsignal sampled over a first time period to determine a first metricindicative of a metabolic state of a myocardium of the subject duringthe first time period; analyzing a second frequency domain transform ofthe electrocardiogram signal sampled over a second time period that issubsequent to the first time period to determine a second metricindicative of the metabolic state of the myocardium of the subjectduring the second time period; comparing the first metric to the secondmetric to determine whether the metabolic state of the myocardium of thesubject is improving; and indicating, responsive to a determination thatthe metabolic state of the myocardium is not improving, administrationof an intervention to the subject.

In accordance with another aspect of the present invention, a method ofdetermining effectiveness of an intervention administered to a subjectis provided. The method comprises receiving an electrocardiogram signalof the subject during administration of the intervention; analyzing afirst frequency domain transform of the electrocardiogram signal sampledover a first time period to determine a first metric indicative of ametabolic state of a myocardium of the subject during the first timeperiod; analyzing a second frequency domain transform of theelectrocardiogram signal sampled over a second time period that issubsequent to the first time period to determine a second metricindicative of the metabolic state of the myocardium of the subjectduring the second time period; and comparing the first metric to thesecond metric to determine whether the metabolic state of the myocardiumof the subject is one of improving, worsening, and remainingsubstantially the same.

BRIEF DESCRIPTION OF DRAWINGS

The accompanying drawings are not intended to be drawn to scale. In thedrawings, each identical or nearly identical component that isillustrated in various figures is represented by a like numeral. Forpurposes of clarity, not every component may be labeled in everydrawing. In the drawings:

FIG. 1 a is a flowchart showing a resuscitation routine that may beperformed to guide resuscitation of a subject experiencing cardiacarrest according to an example embodiment of the invention;

FIG. 1 b is a flowchart of an alternative resuscitation routine that maybe performed to guide resuscitation of a subject experiencing cardiacarrest according to an example embodiment of the invention; and

FIG. 2 is a functional block diagram of an advanced lifesaving devicethat may be used to implement the resuscitation routines of FIGS. 1 aand 1 b according to an example embodiment of the invention.

DETAILED DESCRIPTION

This invention is not limited in its application to the details ofconstruction and the arrangement of components set forth in thefollowing description or illustrated in the drawings. The invention iscapable of other embodiments and of being practiced or of being carriedout in various ways. Also, the phraseology and terminology used hereinis for the purpose of description and should not be regarded aslimiting. The use of “including,” “comprising,” “having,” “containing,”“involving,” and variations thereof herein is meant to encompass theitems listed thereafter and equivalents thereof as well as additionalitems.

As described in the '856 patent, a spectral analysis of VF waveformsobtained from a subject's ECG may be used to predict when defibrillationis likely to be successful in restoring a perfusing cardiac rhythm ofthe subject, as well as to predict when defibrillation is likely to notbe successful in restoring a perfusing cardiac rhythm. Although the '856patent describes a variety of different metrics that may be used topredict the probability of success or failure of defibrillation torestore a perfusing cardiac rhythm, the area of the amplitude spectrum(ASA or AMSA) of the VF waveform has been shown to have a high positivepredictive value (i.e., the ability to correctly predict thatdefibrillation is likely to restore a perfusing cardiac rhythm) as wellas a high negative predictive value (i.e., the ability to correctlypredict that defibrillation is unlikely to restore a perfusing cardiacrhythm). A further advantage of AMSA values as an indicator of theprobability of success or failure of defibrillation is that AMSA valuesmay be determined from an ECG that is obtained during the performance ofchest compressions, and further, the subject's ECG may be filtered(e.g., using a band pass filter with a pass band between approximately 2to 40 Hz) to remove artifacts relating to chest compressions withoutimpacting the predictive capability of the AMSA values calculatedtherefrom.

Applicant has appreciated that a high AMSA value reflects a bettermetabolic state of the myocardial cells. Further, Applicant hasidentified that high quality chest compressions can increase AMSAvalues, as such high quality chest compressions create blood flow to theischemic myocardium, thereby improving its metabolic state. Accordingly,AMSA values may be used as an indicator of the efficacy of chestcompressions, or other forms of intervention, such as the introductionof a metabolite and/or a metabolic enhancing agent, the introduction ofa thrombolytic agent, the electromagnetic stimulation of cardiac tissueat energy levels below those sufficient to defibrillate the heart, orcombinations thereof.

Although high quality chest compressions can create blood flow to anischemic myocardium, they may not be successful in certain situations.For example, some cardiac arrests may be caused by an acute blockage ofa coronary artery (termed acute myocardial infarction). Where an acuteblockage is present, even high quality chest compressions may not besuccessful in restoring blood flow to the region of the myocardium thatis supplied by the blocked vessel because the blockage prevents it.Thus, where an acute blockage is suspected, or where other resuscitationefforts have proven unsuccessful, a thrombolytic agent, such as TissuePlasminogen Activator (TPA) or recombinant TPA (rTPA) may be injected tobreak down or dissolve the blockage. Although the introduction of athrombolytic agent may ultimately dissolve the blockage and permit therestoration of blood flow to the ischemic region of the myocardium, itcannot do so immediately, as the process of thrombolysis generally takestwenty minutes or more. During this time period of time, continued chestcompressions are recommended.

Because AMSA values may be used to identify an improved metabolic stateof myocardial cells due to chest compressions, Applicant has appreciatedthat AMSA values may also be used to identify an improved metabolicstate of myocardial cells due to the re-opening of a blocked vessel.Accordingly, AMSA values as well as other metrics indicative of themetabolic state of a subject's myocardial cells may be used not only topredict the probability of success or failure of defibrillation torestore the subject's perfusing cardiac rhythm, but to identify whenintroduction of a thrombolytic agent should be attempted, as well as toidentify when the thrombolytic agent is achieving success at breakingdown the blockage. In addition, changes in a subject's AMSA values overtime may be used to adjust the amount of thrombolytic agent introduced,the time at which it is introduced, or the manner of introduction (e.g.,bolus or drip).

For example, if, during early application of CPR, it is determined thatchest compressions do not lead to an increase in AMSA values, then thislack of an increase in AMSA values may be viewed as an indication ofvascular blockage, and lysis (i.e., the injection of a thrombolyticagent) may be attempted earlier than it is typically done today (wherelysis is generally used in a last-ditch effort to save the life of asubject), such as when other attempts at resuscitation have provenunsuccessful. After applying lysis, typical CPR cycles may be suspendedand chest compressions performed until AMSA values increase. Such anincrease in AMSA values may be viewed as an indication of the re-openingof a previously blocked coronary vessel. When the AMSA values rise to alevel where the probability of successful defibrillation is indicated,defibrillation may then be attempted. It should be appreciated that bymonitoring AMSA values or other indicators of the metabolic state ofmyocardial cells, defibrillation attempts that are likely to beunsuccessful may be avoided, thereby reducing the cellular damage thatis associated with repeated defibrillation shocks. In addition, theavoidance of defibrillation shocks during periods in which they areunlikely to be successful reduces hands-off time (i.e., the period oftime where chest compressions may be discontinued before and afterdefibrillation in an effort to obtain a clearer ECG without artifacts ofchest compressions, and/or to avoid exposing a rescuer or otheremergency personnel to defibrillating shocks), which further increasesthe subject's chances of survival.

It should be appreciated that AMSA values may be used to identify animproved metabolic state of myocardial cells due to other forms ofintervention, other than the introduction of a thrombolytic agent or theapplication of CPR. Such other forms of intervention may include theintroduction of a metabolite such as aspartate, glucose, nicotinamideadenine dinucleotide (NAD+), proglycogen, or 2-oxoglutarate, theintroduction of a metabolic enhancing agent such as epinephrine,insulin, norepinephrine, etc., the application of electromagnetic energyto stimulate cardiac tissue at energy levels below those sufficient fordefibrillation (termed “microperfusion” herein), or combinationsthereof, such as described in commonly owned published U.S. applicationnumber US2005/0234515, which is incorporated herein by reference in itsentirety.

FIG. 1 a is a flowchart showing a resuscitation routine 100 a that maybe performed to guide resuscitation of a subject experiencing cardiacarrest according to an example embodiment of the invention. Theresuscitation routine 100 a may be performed by a life support device,such as an Advanced Life Support (ALS) defibrillator. During performanceof the resuscitation routine 100 a, chest compressions are continuouslyperformed, except during those periods of time in which defibrillationis applied to the subject. The chest compressions may be performedmanually by emergency responders, or with the aid of a chest compressiondevice, such as the AutoPulse® Non-invasive Cardiac Support Pumpavailable from Zoll Medical Corporation, of Chelmsford, Mass. Where thelife support device is capable of performing defibrillation withoutinterrupting the performance of chest compressions, the chestcompressions may be performed continuously during performance of theresuscitation routine 100 a.

In act 110, after ECG leads are attached to the body of the subject, theresuscitation routine analyzes the ECG of the subject. Analysis that maybe performed in act 110 can include analyzing the ECG signals toidentify whether a regular heart rhythm is detected (in which case, theroutine may immediately terminate as defibrillation is not necessary),and whether a cardiac condition that is treatable by defibrillation(e.g., a ‘shockable’ ECG rhythm such as VT or VF) is present. Where acondition that is treatable by defibrillation is present, act 110 caninclude analyzing the subject's ECG signals over a period of time in themanner described in the '856 patent to determine AMSA values. Ingeneral, subjects with an AMSA value of about 21 mV*Hz have astatistically good chance of survival with typical interventions, thosewith an AMSA value of approximately 12 have about a 50% chance ofsurvival, and those with AMSA values below about 7 are statisticallyunlikely to survive. It should be appreciated that in act 110, metricsother than AMSA values may be determined, such as Power Spectrum Area(PSA) or Average (or Median) peak-to-trough Amplitude (AM), instead orin addition to AMSA values.

In act 120, where a condition that is appropriately treated bydefibrillation is present, the resuscitation routine determines aprobability of successful defibrillation based upon the analysis of thesubject's ECG performed in act 110. The determination made in act 120may be based upon an evaluation of a single metric, such as thesubject's AMSA values, or upon an evaluation of a number of differentmetrics. Where it is determined in act 120 that the probability ofsuccessful defibrillation meets or exceeds a certain threshold, forexample 80%, the routine proceeds to act 130 wherein defibrillation isapplied to the subject.

In act 140, a determination is made as to whether the defibrillationapplied in act 130 was successful. Such a determination may be madebased upon further analysis of the subject's ECG, by monitoring thesubject's respiration, pulse, or other vital signs, or combinationsthereof. Where it is determined in act 140 that defibrillation wassuccessful, the routine may terminate, although it should be appreciatedthat the life support device may continue to monitor the vital signs ofthe subject.

Alternatively, where it is determined in act 120 that no conditiontreatable by defibrillation is present, or that the probability ofsuccessful defibrillation is at or below a certain threshold, forexample, 20%, defibrillation is not performed, and the routine proceedsto act 150. As discussed further below, thresholds other than 80% and20% may be used, such that defibrillation may be performed when theprobability of success is above a determined threshold (e.g., 50%), andnot performed when the probability of success is below the determinedthreshold.

In act 150, the resuscitation routine again analyzes the ECG of thesubject. The analysis performed in act 150 can include identifyingwhether a regular heart rhythm is detected (in which case, the routinemay immediately terminate as defibrillation is not necessary), andwhether a cardiac condition that is treatable by defibrillation (e.g.,VT or VF) is present. Where a condition that is treatable bydefibrillation is present, act 150 can further include analyzing thesubject's ECG signals over a period of time in the manner described inthe '856 patent to determine AMSA values, or other metrics indicative ofthe metabolic state of the subject's myocardium. It should beappreciated that the analysis performed in act 150 may be similar to theanalysis performed in act 110 described above, but it is performed overa period of time that is later than the analysis performed in act 110.Because the analysis performed in act 150 is performed over a differentand subsequent period of time than that performed in act 110, theanalysis performed in act 150 can be compared to the prior analysisperformed in act 110 to detect any improvement, or worsening of themetabolic state of the subject's myocardium. It should be appreciatedthat the difference in time between acts 110 and 150 (or betweensuccessive iterations of act 150) can vary depending upon the type ofintervention being used and the timeframe in which the intervention maybe expected to take effect. In general, the difference in time betweenacts 110 and 150 (or between successive iterations of act 150) wouldtypically be on the order of about 30 seconds to about three minutes, soas to detect changes in the metabolic state of the myocardium.

In act 160, a comparison between the metrics determined in acts 110 and150 (or between successive iterations of act 150 is performed todetermine whether the metabolic state of the subject's myocardium isimproving, remaining substantially the same, or worsening. A number ofdifferent comparisons may be made in act 160, dependent, for example, onthe particular type of intervention, the timeframe in which theparticular type of intervention may be expected to take effect, etc. Forexample, where the type of intervention can be expected to take effectover a relatively short time frame (e.g., a few minutes), a comparisonof the change in AMSA values over time (e.g., the change in AMSA valuesover successive iterations of act 150) may be used to detect whether themetabolic state of the subject's myocardium is improving or not. Such acomparison of the slope of the change in AMSA values over time may beappropriate for interventions such as the administration of metabolitesor metabolic enhancements that generally take effect over shorterdurations of time. For other types of interventions that generally takeeffect over longer durations of time, a different type of comparison maybe used. For example, where the intervention is the administration of athrombolytic agent that may take ten or twenty minutes to take effect,and for which the effects of successful thrombolysis may be reflected asa step increase in AMSA values, a different type of comparison, such aschange point analysis may be used. As known to those skilled in the art,change point analysis is capable of detecting small changes in noisydata with minimal delay and good accuracy, such as would be likelyduring thrombolysis.

Where it is determined in act 160 that the metabolic state of thesubject's myocardium is improving, the routine returns to act 120,wherein acts 120, 150, and 160 may again be performed until theprobability of successful defibrillation meets or exceeds the threshold(act 120) and acts 130 and 140 are performed. Alternatively, where it isdetermined in act 160 that the metabolic state of the subject'smyocardium is not improving (that is, where it is determined that themetabolic state of the subject's myocardium remains essentially thesame, or is worsening), the routine proceeds to act 170.

In act 170 a determination is made as to whether an intervention, suchas the introduction of a thrombolytic agent such as TPA or rTPA, ametabolite, or a metabolic enhancing agent to the body of the subjecthas previously been administered, such as by injection or infusion. Sucha determination may be made by the ALS device visually or audiblyprompting an emergency responder to indicate whether a thrombolyticagent or other type of intervention has been administered and awaiting aresponse. Where it is determined that a thrombolytic agent or other typeof intervention has previously been administered, the routine returns toact 120. The acts described above may be repeated and the subject's ECGrepeatedly analyzed in successive iterations of act 150 to determinewhether the administered thrombolytic agent or other type ofintervention is achieving any success in improving the metabolic stateof the subject's myocardium and to allow the thrombolytic agent or othertype of intervention time to take effect.

Alternatively, where it is determined in act 170 that a thrombolyticagent or other type of intervention has yet to be administered to thesubject, the routine proceeds to act 180, wherein the routine promptsthe emergency responder or other care giver to administer anintervention to the body of the subject. For example, in act 180, theALS device may visually or audibly prompt the emergency responder toadminister a thrombolytic agent, and may even recommend a particulartype of thrombolytic agent and dosage amount, based upon recommendedguidelines and/or the prior analysis of the subject's myocardialcondition. After prompting the emergency responder to administer thethrombolytic agent or other type of intervention, the routine proceedsto act 120 wherein the acts described above may be repeated. The actsdescribed above may be repeated and the subject's ECG repeatedlyanalyzed in successive iterations of act 150 to determine whether theadministered thrombolytic agent or other type of intervention isachieving any success in improving the metabolic state of the subject'smyocardium and to allow the thrombolytic agent or other type ofintervention time to take effect.

It should be appreciated that the resuscitation routine 100 a describedabove is not limited to the acts described above with respect to FIG. 1a, as one or more of the acts may be modified, and other acts may beadded without departing from the scope of the method described herein.For example, after an analysis of the subject's ECG is performed in act110 and a shockable rhythm is detected, the subject may be shockedimmediately in an attempt to restore a regular heartbeat without anydetermination of the probability of success. If this initial attempt atdefibrillation is unsuccessful, the routine may then proceed asdescribed above. Moreover, it should be appreciated that the thresholdsof 80% and 20% used in act 120 are purposefully conservative, and areset to a level to maximize the probability of successful defibrillationwhile minimizing damage to the subject's myocardium, and other valuescould be used. For example, as long as the probability of success wasequal or greater than a certain threshold (e.g., 50%), defibrillationmay be applied, and defibrillation not applied if the probability ofsuccess was less than this threshold. Alternatively, where theprobability of success is less than a first threshold (e.g., 80%) butgreater than a second threshold (e.g., 20%), the routine could audiblyor visually alert the rescuer to the determined probability and requesttheir input on whether to apply defibrillation or not. Where theresuscitation routine is performed by a device that does not have theability to apply defibrillation, such as where the resuscitation routineis performed by a cardiac monitor, act 130 could be modified to audiblyor visually prompt the user (e.g., an emergency responder) to applydefibrillation using a standalone defibrillator.

Other modifications to the resuscitation routine 100 a of FIG. 1 a mayinclude acts of adjusting a level of the intervention that is applied tothe subject in response to the myocardial state of the subjectimproving, or in response to the myocardial state remaining the same, ordeclining. For example, FIG. 1 b is a flowchart showing an alternativeresuscitation routine 100 b that may be performed to guide theresuscitation of a subject experiencing cardiac arrest in which thelevel of intervention administered to the subject may be adjusted basedupon the myocardial state of the subject. As in the resuscitationroutine 100 a described previously with respect to FIG. 1 a, theresuscitation routine 100 b may be performed by a life support device,such as an Advanced Life Support (ALS) defibrillator. During performanceof the resuscitation routine 100 b, chest compressions are performedcontinuously, where such is possible. As the resuscitation routine 100 bof FIG. 1 b is substantially similar to the resuscitation routine 100 aof FIG. 1 a, only the differences are discussed in detail herein.

In act 110, after ECG leads are attached to the body of the subject, theresuscitation routine analyzes the ECG of the subject. Analysis that maybe performed in act 110 can again include analyzing the ECG signals toidentify whether a regular heart rhythm is detected (in which case, theroutine may immediately terminate as defibrillation is not necessary),and whether a cardiac condition that is treatable by defibrillation(e.g., a ‘shockable’ ECG rhythm such as VT or VF) is present. Where acondition that is treatable by defibrillation is present, act 110 caninclude analyzing the subject's ECG signals to determine AMSA values orother metrics, such as Power Spectrum Area (PSA) and Average (or Median)peak-to-trough Amplitude (AM).

In act 120, where a condition that is appropriately treated bydefibrillation is present, the resuscitation routine determines aprobability of successful defibrillation based upon the analysis of thesubject's ECG performed in act 110. The determination made in act 120may be based upon an evaluation of a single metric, such as thesubject's AMSA values, or upon an evaluation of a number of differentmetrics. Where it is determined in act 120 that the probability ofsuccessful defibrillation meets or exceeds a certain threshold, theroutine proceeds to acts 130 and 140 as described previously withrespect to FIG. 1 a.

Alternatively, where it is determined in act 120 that no conditiontreatable by defibrillation is present, or that the probability ofsuccessful defibrillation is at or below a certain threshold,defibrillation is not performed, and the routine proceeds to act 150,wherein the resuscitation routine again analyzes the ECG of the subjectin the manner discussed previously. As previously described with respectto FIG. 1 a, the analysis performed in act 150 may be similar to theanalysis performed in act 110, but it is performed over a period of timethat is later than the analysis performed in act 110.

In act 160, a comparison between the metrics determined in acts 110 and150 (or between successive iterations of act 150) is performed todetermine whether the metabolic state of the subject's myocardium isimproving, remaining substantially the same, or worsening. As notedpreviously with respect to FIG. 1 a, this determination may be basedupon a change in slope of AMSA values over time, or a change pointanalysis of AMSA values, dependent on the type of intervention applied.Where it is determined in act 160 that the metabolic state of thesubject's myocardium is improving, the routine proceeds to act 165wherein a further determination is made as to whether an interventionhas previously been administered (e.g., responsive to act 180 asdescribed below) to the subject. Where it is determined in act 165 thatan intervention has not been administered, the routine returns to act120, wherein acts 120, 150, 160, and 165 may again be performed untilthe probability of successful defibrillation meets or exceeds thethreshold (act 120) and acts 130 and 140 are performed.

Alternatively, where it is determined in act 165 that an interventionhas been administered and is having a beneficial effect (i.e., act 160Yes), the amount of the intervention that is being applied to thesubject may be adjusted in act 167. The adjustment that is made in act167 may be upward or downward, dependent on the type of intervention, aswell as other factors. For example, where the intervention that isrecommended in act 180 is the administration of a thrombolytic agent,such as TPA or rTPA, the recommendation may be to apply a bolus dose ofthe thrombolytic agent to the body of the subject, followed by an IVinfusion at a particular rate, up to a determined maximum dosage. Whereit is determined that the administration of the thrombolytic agent ishaving a beneficial effect (act 160 Yes), the infusion rate of thethrombolytic agent may be reduced or terminated in an effort to reducethe amount of trauma to the subject that results from the thrombolyticproperties of the agent in combination with the physical trauma causedby other resuscitation efforts, such as CPR and defibrillation.Alternatively, where the intervention that is recommended in act 180 isthe administration of metabolite or a metabolic enhancing agent (forexample in a bolus dose followed by an IV drip or infusion at aparticular rate up to a determined maximum dosage), the adjustmentperformed in act 167 may be upward so as to accelerate the improvement,given that such metabolites or metabolic enhancing agents may have fewerand shorter duration side effects. In this manner, AMSA valuesindicative of the metabolic state of a subject's myocardium may be usedto identify whether a particular type of intervention is beingsuccessful, and to guide the amounts and timing used to administer theparticular type of intervention. After adjusting the intervention in act167, the routine returns to act 120, wherein acts 120, 150, 160, 165,and 167 may again be performed until the probability of successfuldefibrillation meets or exceeds the threshold (act 120) and acts 130 and140 are performed.

As with the resuscitation routine 100 a of FIG. 1 a, where it isdetermined in act 160 that the metabolic state of the subject'smyocardium is not improving (that is, where it is determined that themetabolic state of the subject's myocardium remains essentially thesame, or is worsening), the routine proceeds to act 170. In act 170 adetermination is made as to whether an intervention, such as theadministration of a thrombolytic, metabolic, or metabolic enhancingagent to the body of the subject has previously been administered, suchas by injection or infusion. As described previously, such adetermination may be made by the ALS device visually or audiblyprompting an emergency responder or other care giver to indicate whethera thrombolytic agent or other type of intervention has been administeredand awaiting a response. Where it is determined that a thrombolyticagent or other type of intervention has previously been administered,the routine proceeds to act 175.

Where it is previously determined in act 170 that an intervention hasbeen administered (i.e., act 170 Yes) and that intervention does notappear to be having any beneficial effect (i.e., act 160 No), the amountof the intervention that is being applied to the subject may be adjustedin act 175. The adjustment that is made in act 175 may be upward ordownward (or not at all), dependent on the type of intervention, theamount of time for which the intervention has been performed, etc. Forexample, where the intervention that is recommended in act 180 is theadministration of a thrombolytic agent, such as TPA or rTPA, therecommendation may be to apply a bolus dose of the thrombolytic agent tothe body of the subject, followed by an IV infusion at a particularrate, up to a determined maximum dosage. Where it is determined that theadministration of the thrombolytic agent has yet to have a beneficialeffect (act 160 No), the infusion rate of the thrombolytic agent may beincreased, or an additional bolus dose may be provided, up to themaximum dosage. Alternatively, where the maximum dosage has beenreached, or where the amount of time for which the intervention has beenperformed is sufficient to have had a beneficial effect, theintervention may be adjusted downward, or not at all. After adjustingthe intervention in act 175, the routine returns to act 120, whereinacts 120, 150, 160, and any of act 165, 167, 170, and 175 may again beperformed until the probability of successful defibrillation meets orexceeds the threshold (act 120) and acts 130 and 140 are performed. Theacts described above may be repeated and the subject's ECG repeatedlyanalyzed in successive iterations of act 150 to determine whether theadministered thrombolytic agent or other type of intervention isachieving any success in improving the metabolic state of the subject'smyocardium and to allow the thrombolytic agent or other type ofintervention time to take effect.

Alternatively, where it is determined in act 170 that a thrombolyticagent or other type of intervention has yet to be administered to thesubject, the routine proceeds to act 180, wherein the routine promptsthe emergency responder or other medical personnel to administer anintervention to the body of the subject. For example, as previouslydescribed, in act 180, the ALS device may visually or audibly prompt theemergency responder to administer a thrombolytic agent, and may evenrecommend a particular type of thrombolytic agent and dosage amount,based upon recommended guidelines and/or the prior analysis of thesubject' myocardial condition. After prompting the emergency responderto administer the thrombolytic agent or other type of intervention, theroutine proceeds to act 120 where the acts described above may berepeated.

As described with respect to FIG. 1 b above, changes in AMSA values overtime may be used to detect the success (or lack of success) of aparticular type of intervention. Such changes may then be used to adjustthe level, the timing, or both the level and timing at which theparticular type of intervention is being administered (e.g., to adjust adosage of thrombolytic agent being provided to the subject) based on thedetected success (or lack thereof).

As with the resuscitation routine of FIG. 1 a, it should be appreciatedthat the resuscitation routine 100 b described above is not limited tothe acts described above as one or more of the acts may be modified, andother acts may be added without departing from the scope of the methoddescribed herein. For example, where a particular type of interventionis administered and found not to improve the metabolic state of thesubject's myocardium within a timeframe in which it could have, analternative type of intervention may be recommended. Moreover, othermodifications, such as those previously discussed with respect to theresuscitation routine 100 a may also be readily envisioned.

Although the monitoring of AMSA values or other metrics indicative ofthe metabolic state of a subject's myocardium over time may be used toguide resuscitation efforts in the manner discussed above with respectto FIGS. 1 a and 1 b, they may more generally be used as an indicatorfor guiding therapy. For example, AMSA values may be used to monitor asubject's myocardial state and to maintain that state within a desiredrange. For example, one might want to maintain a subject's AMSA valuesat a specific number, or within a specific range of values by deliveringmetabolic agents. The metabolic state of the subject's heart willgenerally increase following the delivery of the metabolic agents, butwill then fall back after a few minutes. However, by monitoring thesubject's AMSA values, the amount and/or timing of the delivery of themetabolic agents may be adjusted so as to maintain the metabolic stateof the subject's heart in a desired state corresponding to a particularrange of AMSA values.

FIG. 2 is a block diagram of an ECG monitoring system that can be usedto monitor and analyze a subject's ECG signal in accordance with theresuscitation routines of FIGS. 1 a and 1 b. The ECG monitoring systemmay be configured for use as a standalone monitor, or integrated into anALS device 200 as shown in FIG. 2.

As shown in FIG. 2, the ALS device 200 includes a processor 210, asensor interface 220, data storage 230, a user interface 240, a therapydelivery interface 250, and a power supply 260. The processor 210, thesensor interface 220, the storage device 230, the user interface 240,and the therapy delivery interface 250 are coupled together via a bus270. The power supply 260 may be a conventional AC to DC power supplycapable of providing power to the other device components, or where theALS device 200 is a portable ALS device, the power supply 260 mayinclude a DC power supply, such as a battery. The data storage 230includes a computer readable and writeable data storage mediumconfigured to store non-transitory instructions and other data (such asAMSA values determined in acts 110 and 150 of FIGS. 1 a and 1 b), andcan include both nonvolatile storage media, such as optical or magneticdisk, ROM or flash memory, as well as volatile memory, such as RAM. Theinstructions may include executable programs or other code that can beexecuted by the processor 210 to perform any of the functions describedabove with respect to the resuscitation routine of FIGS. 1 a and 1 b.

The processor 210 may be any type of processor, microprocessor, orcontroller, such as a microprocessor commercially available from suchcompanies such as Texas Instruments, Intel, AMD, Sun, IBM, Motorola,Freescale, ARM Holdings, etc. In one implementation, the processor is aDSP processor, such as a Freescale DSP56311 Digital Signal Processor,that is capable of performing the acquisition and spectral analysis ofECG signals. The processor 210 is configured to monitor the subject'smedical condition, to perform medical data logging, analysis andstorage, and to provide medical treatment to the subject in response toa detected medical condition, such as cardiac arrhythmia.

The sensor interface 220 couples the at least one processor 210 to aplurality of physiological sensors, such as a plurality of ECG sensingelectrodes 221, 222 that are attached to the body of the subject. Insome embodiments, the sensor interface 220 may also couple the processor210 to other physiological sensors, such as activity sensors, pulseoxygen sensors, temperature sensors, respiratory rate sensors, thoracicimpedance sensors, blood pressure sensors, acoustic sensors, etc. Thesensor interface 220 will typically include one or more amplifiers tobuffer, amplify, and/or filter the ECG signals of the subject. Thesensor interface 210 also includes an Analog to Digital (A/D) converterto sample and digitize the subject's ECG signal and provide thedigitized samples of the subject's ECG signal to the processor 210.Although the sensor interface 220 has been described as includingvarious electronic circuitry capable of buffering, amplifying,filtering, and digitizing the ECG signals of the subject, those ofordinary skill in the art should appreciate that one or more of thosefunctions could alternatively be performed elsewhere in the ALS device200.

The therapy delivery interface 250 couples one or more therapy deliverydevices, such as defibrillator electrodes 251, 252, that may be attachedto the subject's chest, to the processor 210. In an embodiment, thetherapy delivery interface 250 is capable of delivery a biphasicdefibrillating shock to the body of the subject.

The user interface 240 includes a combination of hardware and softwarecomponents that allow the ALS device 200 to communicate with a user,such as an emergency responder. These components are configured toprovide guidance or instruction (visually or audibly) to the user, andto receive information and/or feedback (visually, audibly, or hapticly)from the user. Examples of the components that may be employed withinthe user interface 240 include keyboards, mouse devices, trackballs,microphones, touch-sensitive display screens, conventional displayscreens, and speakers.

In use, the plurality of ECG sensing electrodes 221, 222 and thedefibrillation electrodes 251, 252 are placed on the body of thesubject. Signal processing circuitry within the sensor interface 220buffers, amplifies, and in some embodiments, filters the subject's ECGsignal, and samples of the processed ECG signal are digitized by an A/Dconverter and provided to the processor 210. The processor 210 analyzesthe digitized ECG signal to determine whether a normal cardiac rhythm ispresent, and if not, to determine whether a cardiac condition that istreatable by defibrillation (such as VT or VF) is present. The processor210 may display the digitized ECG signal on a display associated withthe user interface 240. Where the processor 210 determines thattreatable cardiac condition is present, the processor 210 transforms thetime domain samples of the subject's ECG signal to the frequency domain,for example, by using a fast Fourier transform (FFT), and calculates oneor more metrics that based upon an spectral analysis of the transformedECG signal. The metrics that are calculated by the processor 210 mayinclude AMSA values, PSA values, or other metrics indicative of theprobability of successful defibrillation and the metabolic state of thesubject's myocardium. Where the processor determines that theprobability of successful defibrillation is sufficiently high as towarrant the application of a defibrillating shock, the processor 210 mayinstruct the therapy delivery interface 250 to do so. Alternatively,where the probability of successful defibrillation is low, the processormay send a message to be presented by the user interface 240recommending the administration of a thrombolytic agent or other type ofintervention to the subject if one has not been previously administered.

Having thus described several aspects of at least one embodiment of thisinvention, it is to be appreciated various alterations, modifications,and improvements will readily occur to those skilled in the art. Suchalterations, modifications, and improvements are intended to be part ofthis disclosure, and are intended to be within the scope of theinvention. Accordingly, the foregoing description and drawings are byway of example only.

What is claimed is:
 1. A system comprising: a sensor interfaceconfigured to receive and process an analog electrocardiogram signal ofa subject and provide a digitized electrocardiogram signal sampled overa first time period and a second time period that is subsequent to thefirst time period; and a processor, coupled to the sensor interface,configured to: receive the digitized electrocardiogram signal, analyze afrequency domain transform of the digitized electrocardiogram signalsampled over the first time period and determine a first metricindicative of a metabolic state of a myocardium of the subject duringthe first time period, the first metric including an amplitude spectralarea of ventricular fibrillation waveforms of the electrocardiogramsignal sampled over the first time period, determine whether the subjectexhibits a cardiac condition appropriately treatable by defibrillationbased on an evaluation of the first metric; in response to adetermination that the subject does not exhibit a cardiac conditionappropriately treatable by defibrillation, analyze a frequency domaintransform of the digitized electrocardiogram signal sampled over asecond time period and determine a second metric indicative of ametabolic state of a myocardium of the subject during the second timeperiod, the second metric including an amplitude spectral area ofventricular fibrillation waveforms of the electrocardiogram signalsampled over the second time period, compare the first and secondmetrics to determine whether the metabolic state of the myocardium ofthe subject is improving, and to indicate administration of anintervention to the subject in response to a determination that themetabolic state of the myocardium of the subject is not improving. 2.The system of claim 1, further comprising: a therapy delivery interfaceto provide a defibrillating shock to a body of the subject; wherein theprocessor is further configured to instruct the therapy deliveryinterface to apply a defibrillating shock to a the subject in responseto at least one of the first metric and the second metric exceeding apredetermined threshold.
 3. The system of claim 2, wherein thepredetermined threshold is related to a probability of successfuldefibrillation.
 4. The system of claim 1, wherein the processor analyzesthe frequency domain transform of the digitized electrocardiogram signalsampled over a third time period that is subsequent to the first andsecond time periods to determine a third metric indicative of themetabolic state of the myocardium of the subject during the third timeperiod.
 5. The system of claim 4, wherein the processor compares thethird metric to at least one of the second metric and the first metricto determine whether the metabolic state of the myocardium of thesubject is improving.
 6. The system of claim 1, wherein the processordetermines, responsive to a determination that the metabolic state ofthe myocardium of the subject is improving, that the interventionadministered to the subject is achieving success.
 7. The system of claim1, wherein the first metric is an amplitude spectral area of ventricularfibrillation waveforms of the electrocardiogram signal sampled over thefirst time period.
 8. The system of claim 1, wherein the second metricis an amplitude spectral area of ventricular fibrillation waveforms ofthe electrocardiogram signal sampled over the second time period.
 9. Thesystem of claim 1, wherein the indicated administration of theintervention to the subject includes at least one of introduction of athrombolytic agent, introduction of a metabolite, introduction of ametabolic enhancing agent, and application of electromagnetic energy tostimulate cardiac tissue at energy levels below those sufficient fordefibrillation.
 10. A method comprising: receiving an electrocardiogramsignal from a subject; analyzing a first frequency domain transform ofthe electrocardiogram signal sampled over a first time period todetermine a first metric indicative of a metabolic state of a myocardiumof the subject during the first time period, the first metric includingan amplitude spectral area of ventricular fibrillation waveforms of theelectrocardiogram signal sampled over the first time period; determiningwhether the subject exhibits a cardiac condition appropriately treatableby defibrillation based on an evaluation of the first metric; responsiveto determining that the subject does not exhibit a cardiac conditionappropriately treatable by defibrillation, analyzing a second frequencydomain transform of the electrocardiogram signal sampled over a secondtime period that is subsequent to the first time period to determine asecond metric indicative of the metabolic state of the myocardium of thesubject during the second time period, the second metric including anamplitude spectral area of ventricular fibrillation waveforms of theelectrocardiogram signal sampled over the second time period; comparingthe first metric to the second metric to determine whether the metabolicstate of the myocardium of the subject is improving; and indicating,responsive to a determination that the metabolic state of the myocardiumof the subject is not improving, administration of an intervention tothe subject.
 11. The method of claim 10, wherein indicating includesindicating administration of at least one of a thrombolytic agent, ametabolite, a metabolic enhancing agent, and application ofelectromagnetic energy to stimulate cardiac tissue at energy levelsbelow those sufficient for defibrillation to the subject.
 12. The methodof claim 10, further comprising: analyzing a third frequency domaintransform of the electrocardiogram signal sampled over a third timeperiod that is subsequent to the first and second time periods todetermine a third metric indicative of the metabolic state of themyocardium of the subject during the third time period; comparing thethird metric to at least one of the second metric and the first metricto determine whether the metabolic state of the myocardium of thesubject is improving; and determining, responsive to a determinationthat the metabolic state of the myocardium of the subject is improving,that the intervention administered to the subject is achieving success.13. The method of claim 12, further comprising: determining whether thethird metric meets or exceeds a predetermined threshold; and applying adefibrillating shock to the subject responsive to a determination thatthe third metric meets or exceeds the predetermined threshold.
 14. Amethod of determining effectiveness of an intervention administered to asubject, the method comprising: receiving an electrocardiogram signal ofthe subject during administration of the intervention; analyzing a firstfrequency domain transform of the electrocardiogram signal sampled overa first time period to determine a first metric indicative of ametabolic state of a myocardium of the subject during the first timeperiod, the first metric including an amplitude spectral area ofventricular fibrillation waveforms of the electrocardiogram signalsampled over the first time period; determining whether the subjectexhibits a cardiac condition appropriately treatable by defibrillationbased on an evaluation of the first metric; responsive to determiningthat the subject does not exhibit a cardiac condition appropriatelytreatable by defibrillation, analyzing a second frequency domaintransform of the electrocardiogram signal sampled over a second timeperiod that is subsequent to the first time period to determine a secondmetric indicative of the metabolic state of the myocardium of thesubject during the second time period, the second metric including anamplitude spectral area of ventricular fibrillation waveforms of theelectrocardiogram signal sampled over the second time period; andcomparing the first metric to the second metric to determine whether themetabolic state of the myocardium of the subject is one of improving,worsening, and remaining substantially the same.
 15. The method of claim14, further comprising: determining, responsive to a determination thatthe metabolic state of the myocardium of the subject is improving, thatthe intervention is effective.
 16. The method of claim 15, furthercomprising: adjusting an amount of the intervention administered to thesubject in response to determining that the intervention is effective.17. The method of claim 15, wherein the intervention administered to thesubject is at least one of chest compressions, introduction of athrombolytic agent, introduction of a metabolite, introduction of ametabolic enhancing agent, and application of electromagnetic energy tostimulate cardiac tissue at energy levels below those sufficient fordefibrillation to the subject.
 18. The method of claim 17, wherein thefirst metric is an amplitude spectral area of ventricular fibrillationwaveforms of the electrocardiogram signal sampled over the first timeperiod and the second metric is an amplitude spectral area ofventricular fibrillation waveforms of the electrocardiogram signalsampled over the second time period.
 19. The method of claim 14, whereinthe intervention administered to the subject is at least one of chestcompressions, introduction of a thrombolytic agent, introduction of ametabolite, introduction of a metabolic enhancing agent, and applicationof electromagnetic energy to stimulate cardiac tissue at energy levelsbelow those sufficient for defibrillation to the subject.
 20. The methodof claim 14, wherein the first metric is an amplitude spectral area ofventricular fibrillation waveforms of the electrocardiogram signalsampled over the first time period and the second metric is an amplitudespectral area of ventricular fibrillation waveforms of theelectrocardiogram signal sampled over the second time period.
 21. Themethod of claim 10, further comprising: responsive to a determinationthat the metabolic state of the myocardium of the subject is improving:determining whether an intervention has previously been administered tothe subject; and responsive to a determination that an intervention haspreviously been administered to the subject, adjusting the amount ofintervention applied to the subject.
 22. The method of claim 10, furthercomprising: responsive to a determination that the metabolic state ofthe myocardium of the subject is not improving: determining whether anintervention has previously been administered to the subject; responsiveto a determination that an intervention has previously been administeredto the subject, one of adjusting the amount of intervention applied tothe subject and recommending an alternative type of intervention; andresponsive to a determination that an intervention has not previouslybeen administered to the subject, indicating administration of anintervention to the subject.